Diagnosis and Management of Neuromuscular Disorders in Children

The first principle of diagnosis is localization in order to optimize the differential diagnosis and avoid unnecessary testing.

Each year, 1.5 million Americans of all ages are treated for neuromuscular disorders. These often progressive nerve and muscle disorders can be debilitating for patients, causing weakness, paralysis, respiratory distress, and intractable pain.

Pediatricians must be aware of the signs and symptoms of acute neuromuscular disorders in children and adolescents, and be able to effectively manage these conditions and refer patients to specialists as necessary. At the 2014 AAP National Conference & Exhibition, John W. Day, MD, PhD, Professor of Neurology, Pediatrics & Pathology, Stanford University School of Medicine, presented “Pump It Up! Acute Neuromuscular Disorders You Should Not Miss,” an informative talk structured around 4 main elements: what are the acute neuromuscular disorders (NMD); how are they diagnosed; what are the multi-systemic effects; and descriptions of specific NMD.

During his talk, Day focused on several specific neuromuscular disorders, including acute myopathy, neuromuscular junction (NMJ) disorders, acute neuropathies, and acute motor neuropathies.

According to Day, the chief diagnostic principles to be followed for current practice include the recognition that NMD are complex, multi-systemic, and pleomorphic. The first principle of diagnosis is localization in order to optimize the differential diagnosis and avoid unnecessary testing, especially inappropriate muscle biopsies.

If there is motor delay, a serum creatine kinase (CK) should be ordered. This basic test is often neglected. Day said his “pet peeve” is the categorization of transaminases as Liver Function Tests (LFTs). All physicians should be alert to the possibility of muscle disease if moderately elevated AST and ALT values are seen in the absence of abnormalities in other LFTs — bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase (GGT). Electromyography can distinguish radiculopathy from neuropathy and NMJ disorder from muscle abnormalities. In response to a question from the audience asked about elevated CK in viral myositis, Day said this was an excellent point but this type of increase is transient whereas CK is very high in babies with overt neuromuscular disease and never returns to normal.

Day reviewed the basic anatomy, physiology, and diagnostic methods for neuromuscular disorders, including the etiology of the highly characteristic fasciculation (twitching) and the diseases where there is anterior horn cell (AHC) involvement such as ALS and Charcot-Marie-Tooth disease.

He then turned to differentiating the causes of weakness. The hallmark feature for a neuropathic cause is sensory involvement and pain. Neuropathic disorders are diagnosable by the pattern of loss (eg, mononeuropathies are localized). Electrophysiology is a critical diagnostic tool — principally electromyography (EMG) and nerve conduction studies (NCS). Day reminded the audience it is very important to exclude a CNS disorder.

Day reviewed the differential diagnosis procedures for NMJ causes, myopathic causes (acute myopathy is uncommon; usually a subacute or chronic disease), and the channelopathies (eg, hyper- and hypokalemic periodic paralyses and the problematic hyperthyroidism with hypokalemia). He pointed out that task-specific fatigue is a very characteristic clinical feature of NMJ disease.

He then described several case histories, including two cases of familial neuromyotonia, autoimmune neuromuscular junction abnormality, toxic neuromuscular junction abnormality due to botulism, and the motor neuron diseases poliomyelitis and infantile motorneuropathy.

The clinical evaluation, diagnostic testing, and acute management of myasthenia gravis and the relatively common Guillain-Barré Syndrome, and its variants, were also discussed. With respect to motor conduction studies, the conduction velocity is the hallmark test for Guillain-Barré. Intravenous immune globulin (IVIG) is the definitive treatment for this disorder but Day noted that these children don’t usually need chronic infusions but the nerves never get back to normal even if EMG testing shows remyelination. Steroids can be very helpful in reducing pain associated with this disease.

There is a new treatment for the childhood motorneuron disease Spinal Muscular Atrophy (SMA). It is based on SMA gene replacement using intrathecal administration of an antisense oligonucleotide currently in phase 2 clinical trials.

The “take home” messages for diagnosis and treatment of acute weakness in childhood include initial physical examination and history to localize the deficit, electrodiagnosis, serology (especially CK), muscle biopsy (but only when appropriate), supportive care such as ventilatory support and airway maintenance, and definitive treatments such as immunologic agents and, in the future, gene modification.

On a final note, Day said differential diagnosis of acute motor weakness should take into account infectious diseases (eg, polio, Lyme Disease), inflammatory causes, metabolic disorders, toxins (lead, arsenic, ticks, etc), and genetic etiologies.